Episensitization: Defying Time’s Arrow
The development of cancer is driven by complex genetic and epigenetic changes that result in aberrant and uncontrolled cellular growth. Epigenetic changes, in particular, are implicated in the silencing or activation of key genes that control cellular growth and apoptosis and contribute to transform...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-06-01
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| Series: | Frontiers in Oncology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fonc.2015.00134/full |
| _version_ | 1819094634054287360 |
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| author | Bryan eOronsky Arnold eOronsky Michelle eLybeck Neil eOronsky Jan eScicinski Corey eCarter Regina eDay Jose eRodriquez Orengo Maribel eRodriguez-Torres Gary eFanger Tony eReid |
| author_facet | Bryan eOronsky Arnold eOronsky Michelle eLybeck Neil eOronsky Jan eScicinski Corey eCarter Regina eDay Jose eRodriquez Orengo Maribel eRodriguez-Torres Gary eFanger Tony eReid |
| author_sort | Bryan eOronsky |
| collection | DOAJ |
| description | The development of cancer is driven by complex genetic and epigenetic changes that result in aberrant and uncontrolled cellular growth. Epigenetic changes, in particular, are implicated in the silencing or activation of key genes that control cellular growth and apoptosis and contribute to transformative potential. The purpose of this review is to define and assess the treatment strategy of episensitization, or the ability to sensitize cancer cells to subsequent therapy by resetting the epigenetic infrastructure of the tumor. One important facet is resensitization by epigenetic mechanisms, which goes against the norm, i.e., challenges the long-held doctrine in oncology that the reuse of previously tried and failed therapies is a clinically pointless endeavor. Thus, episensitization is a hybrid term, which covers recent clinically relevant observations and refers to the epigenomic mechanism of resensitization. Among the many formidable challenges in the treatment of cancer, the most inevitable is the development of acquired therapeutic resistance. Here, we present the basic principles behind episensitization and highlight the evidence suggesting that epigenetically mediated histone hypoacetylation and DNA hypermethylation events may reverse clinical drug resistance. The potential reversibility of epigenetic changes and the microenvironmental impact of epigenetic control on gene expression may mediate a return to a baseline state of treatment susceptibility. Episensitization is a novel and highly practical management strategy both to prevent the practice of permanent treatment discontinuation with the occurrence of resistance, which rapidly exhausts remaining options in the pharmaceutical armamentarium and to significantly extend patient survival. Accordingly, this review highlights several epigenetic agents including decitabine, vorinostat, entinostat, 5-azacitidine, oncolytic viruses and RRx-001. |
| first_indexed | 2024-12-21T23:30:31Z |
| format | Article |
| id | doaj.art-1f962fc558184111b6175a83d721bc50 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-12-21T23:30:31Z |
| publishDate | 2015-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-1f962fc558184111b6175a83d721bc502022-12-21T18:46:30ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2015-06-01510.3389/fonc.2015.00134139487Episensitization: Defying Time’s ArrowBryan eOronsky0Arnold eOronsky1Michelle eLybeck2Neil eOronsky3Jan eScicinski4Corey eCarter5Regina eDay6Jose eRodriquez Orengo7Maribel eRodriguez-Torres8Gary eFanger9Tony eReid10EpicentRxInterWest PartnersEpicentRxCFLSEpicentRxWalter Reed National Military Medical Center / National Cancer InstituteUniformed Services University of the Health SciencesFundación de InvestigaciónFundación de InvestigaciónEpicentRxMoores Cancer Center, University of California at San Diego (UCSD)The development of cancer is driven by complex genetic and epigenetic changes that result in aberrant and uncontrolled cellular growth. Epigenetic changes, in particular, are implicated in the silencing or activation of key genes that control cellular growth and apoptosis and contribute to transformative potential. The purpose of this review is to define and assess the treatment strategy of episensitization, or the ability to sensitize cancer cells to subsequent therapy by resetting the epigenetic infrastructure of the tumor. One important facet is resensitization by epigenetic mechanisms, which goes against the norm, i.e., challenges the long-held doctrine in oncology that the reuse of previously tried and failed therapies is a clinically pointless endeavor. Thus, episensitization is a hybrid term, which covers recent clinically relevant observations and refers to the epigenomic mechanism of resensitization. Among the many formidable challenges in the treatment of cancer, the most inevitable is the development of acquired therapeutic resistance. Here, we present the basic principles behind episensitization and highlight the evidence suggesting that epigenetically mediated histone hypoacetylation and DNA hypermethylation events may reverse clinical drug resistance. The potential reversibility of epigenetic changes and the microenvironmental impact of epigenetic control on gene expression may mediate a return to a baseline state of treatment susceptibility. Episensitization is a novel and highly practical management strategy both to prevent the practice of permanent treatment discontinuation with the occurrence of resistance, which rapidly exhausts remaining options in the pharmaceutical armamentarium and to significantly extend patient survival. Accordingly, this review highlights several epigenetic agents including decitabine, vorinostat, entinostat, 5-azacitidine, oncolytic viruses and RRx-001.http://journal.frontiersin.org/Journal/10.3389/fonc.2015.00134/fullepigeneticsoncologyEpigenomicResensitizationRRx-001Episensitization |
| spellingShingle | Bryan eOronsky Arnold eOronsky Michelle eLybeck Neil eOronsky Jan eScicinski Corey eCarter Regina eDay Jose eRodriquez Orengo Maribel eRodriguez-Torres Gary eFanger Tony eReid Episensitization: Defying Time’s Arrow Frontiers in Oncology epigenetics oncology Epigenomic Resensitization RRx-001 Episensitization |
| title | Episensitization: Defying Time’s Arrow |
| title_full | Episensitization: Defying Time’s Arrow |
| title_fullStr | Episensitization: Defying Time’s Arrow |
| title_full_unstemmed | Episensitization: Defying Time’s Arrow |
| title_short | Episensitization: Defying Time’s Arrow |
| title_sort | episensitization defying time s arrow |
| topic | epigenetics oncology Epigenomic Resensitization RRx-001 Episensitization |
| url | http://journal.frontiersin.org/Journal/10.3389/fonc.2015.00134/full |
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